Menefee, Shawn A. MD; Dyer, Keisha Y. MD; Lukacz, Emily S. MD; Simsiman, Amanda J. MD; Luber, Karl M. MD; Nguyen, John N. MD
From the Department of Obstetrics and Gynecology, Kaiser Permanente San Diego, the Department of Reproductive Medicine, University of California San Diego, and the Department of Obstetrics and Gynecology, Naval Medical Center San Diego, San Diego, California; and the Department of Obstetrics & Gynecology, Kaiser Permanente Downey, Downey, California.
Supported by an unrestricted educational grant from Boston Scientific (Natick, MA).
The authors thank Jasmine Tan-Kim, MD, for her illustration.
Presented at the American Urogynecologic Society annual meetings, September 24–26, 2009, Hollywood, Florida, and September 29-October 2, 2010, Long Beach, California. Presented as a poster at the International Continence Society annual meetings, September 29-October 3, 2009, San Francisco, California, and August 23–27, 2010, Toronto, Canada. Presented as a poster at the American College of Obstetricians and Gynecologists Annual Meeting, San Francisco, California, May 15–19, 2010.
Corresponding author: Shawn A. Menefee, MD, 3250 Fordham Street, Department of Obstetrics & Gynecology, San Diego, CA 92110; e-mail: firstname.lastname@example.org.
Financial Disclosure Dr. Lukacz has received a research grant from Renew Medical. She has served as a consultant for Pfizer and Ethicon/Johnson & Johnson. Dr. Nguyen has received a grant from American Medical Systems. The other authors did not report any potential conflicts of interest.
Women in the United States have an 11% lifetime risk of undergoing surgery to correct pelvic organ prolapse1 and many of these procedures include correction of anterior vaginal wall defects.2 Although originally described by described by Kelly in 1913 as a procedure to treat urinary incontinence,3 anterior colporrhaphy has become the procedure of choice to correct anterior vaginal wall prolapse. Recurrence rates as high as 40% and reoperation rates up to 30% of these treatment failures4–6 have led some surgeons to perform mesh or graft-reinforced repairs.
The heterogeneity of published studies limits the ability to draw reliable conclusions regarding the use of grafts and mesh for prolapse repairs.7–9 Recent data suggest that the use of polypropylene-augmented repairs offers better anatomic support at 1 year than native tissue repair.10–13 However, these studies use “trocar-guided” mesh kits and are limited by short-term follow-up. Additionally, there has been significant concerns raised regarding the long-term safety of synthetic mesh placed vaginally for prolapse repair leading to an U.S. Food and Drug Administration warning (July 2011). Thus, the use of biologic grafts has been advocated; however, data on efficacy for anterior vaginal prolapse repair are limited.7,8,14,15
The aim of our study was to estimate the effect of augmented repairs with permanent mesh or biologic graft compared with a native tissue repair in the absence of confounding issues related to trocar delivery systems. To accomplish this, we designed a randomized double-blind clinical trial comparing traditional anterior colporrhaphy with vaginal paravaginal repairs using porcine dermis graft or permanent synthetic polypropylene mesh.
MATERIALS AND METHODS
This study was undertaken after obtaining approval from the Kaiser Permanente institutional review board. Participants were recruited from the Female Pelvic Medicine and Reconstructive Surgery Clinics at Bellflower and San Diego Medical Centers between January 2006 and September 2008. The study participants were women older than 18 years of age with at least stage II anterior vaginal wall prolapse who were symptomatic, desired surgical correction, and were willing to be randomly assigned to one of three treatment arms. The procedures were performed at two teaching centers and supervised or performed by four fellowship-trained female pelvic medicine and reconstructive surgeons, all with extensive experience in the study procedures. Surgical techniques were standardized between sites. Exclusion criteria included current pregnancy, plans for future pregnancy, a foreshortened vagina (as defined by a total vaginal length of 5 cm or less), a history of vaginal cancer, pelvic irradiation, an adverse reaction to porcine or synthetic materials, a history of graft-reinforced or mesh-reinforced anterior repair, or plans to move outside of the study area within the next 24 months. Concomitant procedures were permitted and performed as medically indicated.
Demographic data included patient's age, ethnicity, body mass index, and pregnancy history. Medical and surgical history was also obtained including all prior urogynecologic procedures with the number, type, and route of each clearly stipulated. Subjective information was also gathered using three validated condition specific questionnaires. The short forms of the Pelvic Floor Distress Inventory, the Pelvic Floor Impact Questionnaire, and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire were all obtained at baseline as well as 12 and 24 months postoperatively.16,17 Objective measures included a pelvic organ prolapse-quantification (POP-Q) examination performed by a blinded examiner.18
Patients were randomized through a computer-generated randomization sequence to: 1) standard anterior colporrhaphy through midline plication; 2) paravaginal repair with porcine dermis graft; or 3) paravaginal repair with polypropylene mesh. Group assignments were in sealed opaque envelopes that were opened by the primary surgeon on the day of surgery in the operating room.
Antibiotic prophylaxis was administered before incision and sequential compression stockings were placed before induction of anesthesia. A vasoconstricting solution was injected along the anterior vaginal wall in those patients without contraindications. The epithelium was incised longitudinally and dissected off the underlying superficial fibromuscular layer. For the colporrhaphy group, a midline plication was performed with interrupted delayed absorbable sutures (2-0 polydioxanone), the epithelium was reapproximated with 2-0 polyglactin, and a vaginal packing was placed.19
If an augmented repair was assigned, hydrodissection followed by dissection of the epithelium off the deep underlying fibromuscular layer and carried out to the level of the ischial spine and arcus tendinous fascia pelvis bilaterally. The Capio suture device was used to place three equidistant 0 polypropylene sutures through the arcus on each side starting just above the ischial spine. The polypropylene mesh or porcine graft was fashioned in a trapezoidal configuration with the base attached at the level of the ischial spines and then narrowing as the graft approached the bladder neck with a typical width of 6–8 cm distally and 12 cm proximally and a length of approximately 4–6 cm based on the patient's anterior vaginal wall and bi-ischial diameter to allow tension-free placement of the secured mesh (Fig. 1). The sutures were then passed through the lateral aspects of the mesh or graft and tied down, thus approximating it to the arcus bilaterally. Finally, the epithelium was reapproximated with 2-0 polyglactin suture and a vaginal packing was placed. Concomitant procedures were performed at the surgeon's discretion for management of stress urinary incontinence and apical and posterior wall prolapse. The mesh or porcine graft was not attached to the apical suspension. When indicated, the apical suspension was performed either vaginally or laparoscopically to only suspend the vaginal apex meant to provide level one support. Intraoperative data including operative time and estimated blood loss were collected as well as information regarding postoperative complications. To avoid unblinding of the patients in the immediate postoperative period, the operative report listed the procedure as cystocele repair per protocol and nursing staff were instructed not to discuss details of the study procedure with the patients. All patients remained in the hospital for at least one night or longer as clinically indicated. Patients were evaluated for urinary retention before discharge.
Routine postoperative evaluation was performed at 6 weeks by the operating surgeon. Outcomes were assessed 12 and 24 months postoperatively using POP-Q examination data and validated questionnaires (Pelvic Floor Distress Inventory, Pelvic Floor Impact Questionnaire, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). A blinded certified examiner (a female pelvic medicine and reconstructive surgery nurse practitioner, fellow, or staff physician) who was not present at the surgery performed objective measures in a standardized fashion.
The primary outcome measure was anatomic failure defined as anterior POP-Q at stage II or greater (Ba measurement of −1 or greater). Secondary outcomes included effect on quality of life (Pelvic Floor Impact Questionnaire), degree of bother (Pelvic Floor Distress Inventory), and sexual symptoms (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire). Composite failure was defined as complaint of “bulge” by a positive response of yes on question 3 of the Pelvic Organ Prolapse Distress Inventory and stage II or greater anterior prolapse.
Power analyses were based on previous published failure rates of 50% for standard anterior colporrhaphy compared with 10% for anterior vaginal wall repair using polypropylene mesh and porcine dermis.9,7,8,14,15,,20–23 Assuming a two-sided hypothesis test with a 5% type I error and 80% power, it was estimated that 25 patients in each group would be required to detect an absolute difference of 40% or more in anatomic success rates between a reinforced procedure and standard colporrhaphy. Assuming a 25% dropout rate, a total of 99 patients were necessary, 33 in each group.
Statistical analysis was performed using SPSS software 11.0. The proportion of patients with anatomic success was compared across groups using χ2 statistics. Median quality-of-life scores were compared using Mann-Whitney U test. Student's t tests were used for continuous variables and χ2 or Fisher's exact tests were used for categorical factors to analyze demographics and baseline characteristics. The manufacturer of the synthetic mesh or porcine graft did not provide the products used in this trial and had no involvement in the study design, data collection or analysis, the writing of the article, or the decision to submit the results for publication.
A total of 99 women were randomized to one of the three treatment arms: 32 to standard anterior colporrhaphy, 31 to porcine dermis graft, and 36 to polypropylene mesh (Fig. 2). Seventy-eight women (79%) completed a minimum of 2 years follow-up. Overall the mean age of all patients was 63±10 years with a median of stage III anterior prolapse (range, II–IV) at baseline with all Ba points 0 or greater. The majority of women had not undergone any prior corrective surgery for the anterior vaginal wall with only 6% reporting a history of anterior repair. Concomitant procedures were common with 40% having hysterectomies, 56% having midurethral slings, and 67% having apical procedures at the time of the study procedure. There were no statistically significant differences in baseline characteristics, clinical history data, concomitant procedures, and perioperative secondary outcomes with the exception of age in the mesh compared with porcine groups (Table 1). Two surgeons (S.M. and J.N.), one at each site, performed the majority of the procedures and less than 4% were performed by two other staff surgeons.
The anatomic failure rate (POP-Q stage II or greater) for polypropylene mesh (18%) was significantly lower than both anterior colporrhaphy (58%, P=.002) and porcine dermis groups (46%, P=.015) with no statistical difference between porcine and colporrhaphy groups (P=.430) (Table 2). The intention-to-treat analysis revealed similar results. With all missing data designated as failures, failure rates were: 36% for mesh, 55% for porcine, and 69% for colporrhaphy.
All groups had a reduction in their prolapse and urinary symptom severity and degree of bother without significant differences between groups as measured by the urinary and prolapse subscales of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire (Table 2). In addition, there were no differences in sexual function as measured by the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire 12.
The composite failure rate (a measure which included objective and subjective definition) was 7% and similar for all three repair types with three in the colporrhaphy (13%), three in the porcine (12%), and one (4%) in the mesh group. Since protocol development, some authors have recommended less stringent definitions of anatomic success (at or beyond the hymen); therefore, we analyzed the data using both Ba point of −1 and 0 for comparison and found no difference between groups (Table 3). All failures were stage II with the exception of a single patient in the porcine group who had stage III prolapse. The two patients who elected to undergo reoperation for recurrent anterior wall prolapse were in the porcine group.
There was no difference between groups with respect to operative time (data not shown); there was a tendency toward a lower estimated blood loss in the colporrhaphy group (Table 1), but no blood transfusions occurred. Stress urinary incontinence requiring treatment occurred in three patients; none of which had synthetic mesh placed (two in the porcine group and one in the colporrhaphy arm).
Erosion rates were higher in the mesh group compared with the porcine group (14% compared with 4%, P=.413). In the mesh group, three patients were asymptomatic and were placed on estrogen vaginal cream; the other two required excision in the operating room. The one erosion in the porcine group healed spontaneously with vaginal estrogen therapy. There were no intraoperative bladder or urethra injuries and no serious adverse events.
Among individuals who were sexually active at baseline without dyspareunia, only seven patients developed new-onset dyspareunia postoperatively. De novo dyspareunia was equally distributed among groups (three in the colporrhaphy group, two in the mesh group, and two in the porcine dermis group; Fig. 3). Furthermore, of the 12 patients who had baseline dyspareunia, nine reported resolution of this symptom postoperatively, and all of the patients who were not sexually active at baseline (n=6) became active postoperatively without dyspareunia.
Successful treatment of anterior vaginal prolapse remains one of the most challenging aspects of pelvic reconstructive surgery. Although anterior colporrhaphy is commonly used to correct anterior vaginal prolapse, high recurrence rates have been consistently reported.9,20 This high failure rate has led to increased use of biologic and synthetic materials in the surgical correction of anterior vaginal prolapse.
Although the placement of synthetic mesh to reinforce prolapse repair has been described in the literature, it has mainly been in the form of nonrandomized trials, often with short follow-up intervals and nonvalidated questionnaires until recently.21–23 Recent randomized trials comparing the use of trocar-based mesh kits with native tissue repairs suggest that the former is associated with better short-term anatomic support without significant differences in subjective symptoms or reoperation rates.10,12 Our freehand polypropylene mesh paravaginal repair technique also demonstrates fewer anatomic failures than anterior colporrhaphy. Although similar success has been reported with mesh,10,12 our follow-up is longer with 2-year outcomes. Altman et al reported longer operative time, increased rate of bladder perforation, and inguinal pain in the mesh group compared with the colporrhaphy group.10 Although we found no difference with respect to operative time in our study, the lack of bladder perforation and inguinal pain is likely related to the fact that we did not use trocar-based mesh placement. Nevertheless, we did note a similar tendency toward an increased estimated blood loss with mesh or graft placement that is likely related to the dissection.
Xenografts also show promise for anterior vaginal wall prolapse with reported cure rates between 78% and 93% with the use of Pelvicol with a lower reported risk of erosion.7,8,14,15,24,25 Based on these findings, we felt that Pelvicol should be compared directly with standard anterior repair. The porcine graft augmentation was inferior to mesh with respect to the anatomic result and did not appear to offer any added benefit over colporrhaphy in terms of symptoms or our composite measure.
A randomized prospective comparison of standard anterior repair and graft or mesh augmented procedures performed using a suture-based technique (in the absence of blind trocar passes) provides an ideal means to assess the inherent differences in success rates and adverse events. Our analysis, with 2-year follow-up, demonstrates that polypropylene mesh-reinforced repairs have significantly fewer anatomic failures than both anterior colporrhaphy and those with porcine dermis augmentation. Although objective failure rates were lower in those patients who received mesh-augmented repair, it is important to note that the only patients who had any reoperations were in the graft or mesh groups.
Barber et al recently reported recommendations for establishing a clinical definition of success that includes the resolution of bulge symptoms and a leading edge of prolapse at or above the hymen.26 Despite the significant difference in anatomic success rates using our stringent definition, the rate of symptomatic recurrence and composite failure was not different between the groups. When we used less stringent definitions of success, the difference noted between groups did not persist. These findings are consistent with Barber's most recent work, which reanalyzed the randomized trial by Weber et al in 2001, which showed that when contemporary clinically relevant definitions of success are used, colporrhaphy offers comparable success rates to mesh-reinforced repair.27 Likewise, all groups experienced an improvement in prolapse and incontinence symptoms as measured by the prolapse and urinary subscales of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire. There was no difference between groups with respect the degree of change in their scores pretreatment and posttreatment. All of this suggests, although our rigorous definition of anatomic failure (POP-Q stage II or greater) is responsible for the difference in failure rates reported, this finding may not translate to patient-centered outcomes and degree of satisfaction when a composite outcome is considered.
We noted that there was no difference preoperatively and postoperatively with respect to Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores regardless of group assignment. Most of our patients were sexually active at baseline, and only seven developed de novo dyspareunia postoperatively and were distributed equally among the three treatment groups. The low rate of de novo dyspareunia rates may be related to the absence of mesh arms present in many mesh kits. Our trial used a wide trapezoid mesh with direct attachment to the arcus using suture only. Although these findings require further investigation, they are promising given that sexual dysfunction has always been a major concern when performing prolapse surgery.
This study was subject to several limitations, including the small sample size. This analysis did not reveal any significant difference between the xenograft and the anterior repair groups. Follow-up may have not been long enough to detect a significant difference in reoperation rates among the treatment groups. In addition, the large majority of patients underwent other reconstructive and anti-incontinence procedures at the time of their anterior vaginal wall repair and thus may represent confounding factors contributing to the improvement in objective and subjective outcomes; however, with randomization, these factors should be minimized. Furthermore, anterior vaginal wall prolapse often occurs in conjunction with other pelvic floor disorders and thus corrective surgery typically requires additional prolapse and anti-incontinence procedures. Two surgeons performed the majority of the procedures, which limits the generalizability to some degree; however, this may be offset by the involvement of trainees in the majority of these cases. Lastly, this study was not powered to detect differences in subjective outcomes among treatment groups. Future studies either powered to detect differences in subjective symptoms or that use composite definitions to assess outcomes as suggested by Barber et al26 are required.
The principle strength of this study is that it is a randomized controlled trial using validated pelvic floor outcome measures and that is double-blinded to participant and examiner. All procedures used suture-based techniques for anterior prolapse repair, eliminating the potential confounding effects of blind trocar passes and mesh arms, which may be associated with certain adverse events such as injuries to surrounding structures (bladder, bowel, vascular, nerve), new-onset dyspareunia, and vaginal pain. Cost analyses need to be performed comparing traditional vaginal paravaginal repair with mesh compared with mesh kits, because significant cost savings may be an advantage of a suture-based repair.
The purpose of our study was to compare the objective success rates and effect on quality of life of three different anterior vaginal wall repairs (anterior colporrhaphy, vaginal paravaginal repair with Pelvicol, and vaginal paravaginal repair with Polyform) in a prospective double-blind randomized trial. Our analysis suggests that placement of polypropylene mesh leads to less anterior compartment anatomic failures with an acceptable complication profile in the short term. Likewise, subjective improvements in urinary and prolapse symptoms as measured by validated instruments were noted in all groups after reconstructive surgery with no significant difference between groups. With careful patient education regarding the risks and benefits of the various approaches to correct anterior wall prolapse, mesh placement may be considered for both new cases and recurrent prolapse repair in patients willing to accept the potential complications to achieve a higher rate of anatomic success.
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